Human embryonic stem cells are cloned

May 15, 2013
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The first step during cloning is removal of chromosome genetic material from a human egg. A hole is made in the egg's shell and a pipette (on the right) slowly remove the chromosomes from the center of the egg. / Cell, Tachibana et al.

by Dan Vergano, USA TODAY

by Dan Vergano, USA TODAY

An international research team has achieved a scientific first by producing embryonic stem cells from cloned embryos, advancing the effort to generate replacement tissues for sick patients.

Embryonic stems cells are the starter cells to all others in the body, which means potentially they can grow into any type of tissue, from blood to bone to brain. For a decade-and-a-half, they have been seen as a potential source of rejection-free transplant tissues for ailments ranging from diabetes to paralysis. They were also the subject of a fierce political fight over the medical ethics of using human embryos in research during the Bush administration because the embryos had to be destroyed in the process of retrieving the embryonic cells.

"We have now refined the steps to come up with a process for generating these cells that is pretty efficient," says Shoukhrat Mitalipov of Oregon Health & Science University in Beaverton, who headed the cell cloning study released by the journal Cell. "There is no one trick to making this work. It is like winning the lottery, all the numbers have to line up the right way to win."

The study team reports a number of steps perfected in monkeys allowed them to take eggs donated by women volunteers and successfully implant the chromosomes taken from skin cells of other people into the eggs. They successfully start the fused egg growing and dividing to become a human embryo. The cells of these embryos were as a result, genetic copies, or clones, of the cells of three different people who donated the skin cells, one of them a patient afflicted with a genetic disorder called Leigh syndrome.

In a first, Mitalipov and his privately funded team report that these cloned embryos were grown past an eight-cell size (where earlier attempts had stopped) into a full-blown early embryo, containing hundreds of embryonic stem cells. Embryonic cells taken from these cloned embryos were grown into six colonies of cells, the first successfully grown cloned human embryonic stem cells. The embryos were destroyed in the cell collection process.

Some of the cells were successfully prompted to become more specialized skin and heart cells. That is the next step in someday using the cells in "regenerative" medicine, where cells cloned from a patient would be used to grow into transplant organs to treat diseases and injuries such as paralysis.

"For stem cell biology, there will be history before this result and then history after it with the study as the dividing line," says stem cell researcher Paul Knoepfler of the University of California, Davis. "No doubt This is a real milestone."

Since 1998, when a University of Wisconsin team first isolated embryonic stem cells grown from a human embryo, researchers have sought to use cloning techniques to create such cells that would be genetic copies of ones belonging to sick patients. The same cloning techniques, which essentially place a new set of genes into a hollowed-out egg, and then kick-start the combination to start dividing and become an embryo, have been used since the cloning of "Dolly the Sheep" in 1996. That helped to create genetic copies, twins, of animals ranging from prize bulls to an extinct kind of wild goat. In those cases, the embryos were implanted into a surrogate mother instead of being destroyed to harvest stem cells.

Knoepfler warned that fertility clinic operators outside the USA might try to replicate the team's method to try to clone a human baby. However, Mitalipov says that his team's technique would not likely create a cloned embryo that could be implanted into a surrogate mother's womb and lead to a pregnancy. "The embryos we produce this way did not lead to pregnancy in monkeys," he says. "We think there is something in the manipulations to make them that make a successful pregnancy impossible."

Attention has drifted away from these once hotly contested embryonic stem cells since 2007, with the rise of "induced" stem cells. Those are grown using gene alterations to regular cells to become near-copies of embryonic stem cells, without the need for embryos. There have also been repeated failures (in one famous case, outright academic fraud by a South Korean researcher) to grow cell lines from cloned human embryos, until now.

With the announcement, a race of sorts starts between those who produce induced stem cells and cloned cells to see which type can most safely be grown into transplant tissues, Knoepfler suggests. Hundreds of researchers are working with induced stem cells, seeking ways to grow them into viable transplant tissues. Two clinical trials are underway sponsored by Advanced Cell Technology of Marlborough, Mass., that use retinal cells grown from embryonic stem cells to treat eye disease. The cells in those pilot trials are not cloned copies of the patient's cells.

The real significance of the advance may be to re-ignite debate over human cloning, says bioethicist Insoo Hyun of Case Western Reserve University in Cleveland.

"Basically, FDA has jurisdiction over clinical research using cloning technology to create a human being," says the Food and Drug Administration's Curtis Allen. "To date, FDA has not licensed such a therapy."

"No legitimate scientists would want to use this technology for reproductive purposes," says stem cell expert George Daley of Children's Hospital Boston. "They would see it not only as unethical, but unsafe and probably illegal."

Still, "This study shows that human cloning can be done," said Richard Doerflinger of the U.S. Conference of Catholic Bishops, which opposes research that destroys embryos."The more important debate is whether it should be done."

Doerflinger points to advances in induced stem cells, created without controversy, as a reason for leaving cloned stem cells on the shelf. "If these cells are the answer, then what was the question," he asks.

Mitalipov, however, points to genetic abnormalities seen in induced stem cells that are absent from embryonic ones. He also cites the clinical trials already approved for embryonic-derived cells that set an easier regulatory path for them to be tested on patients, as reasons why cloned cells might prove more useful to patients than induced stem cells in some cases. "We would like to see other labs confirm our work as well," he says, noting that outside labs have already requested copies of the cloned cells. Because of federal regulations, the cells are not eligible for research funding from the National Institutes of Health, which now lists 209 embryonic stem cell cell "lines" on its research funding registry.